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Involvement of two microRNAs in the early immune response to DNA vaccination against a fish rhabdovirus
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Involvement of two microRNAs in the early immune response to DNA vaccination against a fish rhabdovirus
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Involvement of two microRNAs in the early immune response to DNA vaccination against a fish rhabdovirus
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Journal Article
Involvement of two microRNAs in the early immune response to DNA vaccination against a fish rhabdovirus
2015
Overview
•Two microRNAs (miR-462/-731) are upregulated in fish immunized with a DNA vaccine.•miR-462 and miR-731 were also induced by poly I:C and interferons.•Inhibiting miR-462 and miR-731 reduced the protective effect of poly I:C.•miR-462 and miR-731 directly contribute to interferon-mediated protection.
Mechanisms that account for the high protective efficacy in teleost fish of a DNA vaccine expressing the glycoprotein (G) of Viral hemorrhagic septicemia virus (VHSV) are thought to involve early innate immune responses mediated by interferons (IFNs). Microribonucleic acids (miRNAs) are a diverse class of small (18–22 nucleotides) endogenous RNAs that potently mediate post-transcriptional silencing of a wide range of genes and are emerging as critical regulators of cellular processes, including immune responses. We have recently reported that miR-462 and miR-731 were strongly induced in rainbow trout infected with VHSV. In this study, we analyzed the expression of these miRNAs in fish following administration of the DNA vaccine and their potential functions. Quantitative RT-PCR analysis revealed the increased levels of miR-462, and miR-731 in the skeletal muscle tissue at the site of vaccine administration and in the liver of vaccinated fish relative to empty plasmid backbone-injected controls. The increased expression of these miRNAs in the skeletal muscle correlated with the increased levels of the type I interferon (IFN)-inducible gene Mx, type I IFN and IFN-γ genes at the vaccination site. Intramuscular injection of fish with either type I IFN or IFN-γ plasmid construct resulted in the upregulation of miR-462 and miR-731 at the site of injection, suggesting that the induction of these miRNAs is elicited by IFNs. To analyze the function of miR-462 and miR-731, specific silencing of these miRNAs using anti-miRNA oligonucleotides was conducted in poly I:C-treated rainbow trout fingerlings. Following VHSV challenge, anti-miRNA-injected fish had faster development of disease and higher mortalities than control fish, indicating that miR-462/731 may be involved in IFN-mediated protection conferred by poly I:C.
Publisher
Elsevier Ltd,Elsevier Limited
Subject
/ Animals
/ Cloning
/ DNA
/ Fish
/ genes
/ Glycoproteins - administration & dosage
/ Hemorrhagic Septicemia, Viral - immunology
/ Hemorrhagic Septicemia, Viral - prevention & control
/ Interferon Type I - genetics
/ Interferon Type I - immunology
/ Interferon-gamma - immunology
/ liver
/ microRNA
/ Novirhabdovirus - immunology
/ Oncorhynchus mykiss - immunology
/ Plasmids
/ Poly I-C - administration & dosage
/ Proteins
/ reverse transcriptase polymerase chain reaction
/ Vaccines
/ Vaccines, DNA - administration & dosage
/ Viral hemorrhagic septicemia virus
/ Viral hemorrhagic septicemia virus (VHSV)
